The prognosis of patients with malignant neuroectodermal tumors is poor despite radiation and chemotherapy. Alternative approaches to cancer therapy have focused on the use of biological response modifiers (BRMs) as antitumor agents. Interleukin-2 (IL-2) can activate a subpopulation of cytotoxic lymphocytes termed lymphokine-activated killer (LAK) cells. The systemic administration of autologous LAK cells and IL-2 was shown clinically, to generate an antitumor response, albeit with significant toxicity. Due to the systemic toxicity of IL-2, other modes of IL-2 administration may be more efficacious with lesser toxicity, such as intracavitary or regional. In a phase I trial at the NINCDS, single doses of autologous LAK cells or escalating doses of IL-2 were injected intracerebrally following surgical tumor debulking (one patient received both). No toxicity or neurological deficits due to treatment were noted. A maximally therapeutic regimen of IL-2/LAK would require prolonged, periodic IL-2 administration. This Phase I protocol is designed to examine the acute and cumulative toxicity of escalating doses of IL-2 given in combination with autologous LAK cells activated ex vivo with IL-2. Fifteen (15) patients will be entered in the Phase I study, 3 patients per dose level; accrual to be complete within a year. Leukapheresis will be used to obtain autologous leukocytes. These cells will be readministered as activated LAK cells with IL- 2 on the first day of treatment, via an Ommaya reservoir implanted at the time of reoperation. Additional IL-2 alone will be given for a total of 3x weekly for 2 weeks to complete a single cycle. A second cycle of LAK/IL-2 therapy will be given following a 2 week period for evaluation. Based on determination of a maximal tolerated dose of IL-2, a Phase II trial to evaluate antitumor efficacy will be performed. A total of 30 patients will be entered during years 2 and 3 of this study. Following the initial, post-operative cycles of therapy, patients showing stable disease or response to treatment, will be retreated at 3 month intervals.
| Hayes, R L; Koslow, M; Hiesiger, E M et al. (1995) Improved long term survival after intracavitary interleukin-2 and lymphokine-activated killer cells for adults with recurrent malignant glioma. Cancer 76:840-52 |
